Febuxostat, 2-(3-cyano-4-isobutyloxyphenyl)-4-methylthiazole-5-carboxylic acid, having the following formula:
is a xanthine oxidase (XO) inhibitor indicated for the chronic management of hyperuricemia in patients with gout. Febuxostat is not recommended for the treatment of asymptomatic hyperuricemia. Febuxostat is administrated in the form of tablets that are marketed in the USA and the EU under the name ULORIC®.
PCT publication no. WO 1992/109279 describes Febuxostat. PCT publication no. WO 1999/065885, PCT publication no. WO 2003/082279, PCT publication no. WO 2008/067773, CN 100546985, CN 101139325, CN101085761, CN 101412700, CN 101386605, CN101648926, CN 101671314, CN 101684107 and Hetrocycles, 47, 2, 857-864 describe crystalline forms of Febuxostat including forms A, B, C, D, G, H, I, J, K and M, as well as an amorphous form.
The present invention relates to the solid state physical properties of Febuxostat, 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid. These properties can be influenced by controlling the conditions under which 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid is obtained in solid form.
Polmorphism, the occurrence of different crystal forms, is a property of some molecules and molecular complexes. A single molecule may give rise to a variety of polymorphs having distinct crystal structures and physical properties like melting point, thermal behaviours (e.g. measured by thermogravimetric analysis—“TGA”, or differential scanning calorimetry—“DSC”), X-ray diffraction pattern, infrared absorption fingerprint, and solid state NMR spectrum. One or more of these techniques may be used to distinguish different polymorphic forms of a compound.
Discovering new polymorphic forms and solvates of a pharmaceutical product can provide materials having desirable processing properties, such as ease of handling, ease of processing, storage stability, ease of purification or as desirable intermediate crystal forms that facilitate conversion to other polymorphic forms. New polymorphic forms and solvates of a pharmaceutically useful compound can also provide an opportunity to improve the performance characteristics of a pharmaceutical product. It enlarges the repertoire of materials that a formulation scientist has available for formulation optimization, for example by providing a product with different properties, e.g., better processing or handling characteristics, improved dissolution profile, or improved shelf-life. For at least these reasons, there is a need for additional polymorphs of Febuxostat.